Timing along the cardiac cycle modulates neural signals of reward-based learning.

Natural fluctuations in cardiac activity modulate brain activity associated with sensory stimuli, as well as perceptual decisions about low magnitude, near-threshold stimuli. However, little is known about the relationship between fluctuations in heart activity and other internal representations. Here we investigate whether the cardiac cycle relates to learning-related internal representations - absolute and signed prediction errors. We combined machine learning techniques with electroencephalography with both simple, direct indices of task performance and computational model-derived indices of learning. Our results demonstrate that just as people are more sensitive to low magnitude, near-threshold sensory stimuli in certain cardiac phases, so are they more sensitive to low magnitude absolute prediction errors in the same cycles. However, this occurs even when the low magnitude prediction errors are associated with clearly suprathreshold sensory events. In addition, participants exhibiting stronger differences in their prediction error representations between cardiac cycles exhibited higher learning rates and greater task accuracy

Transcranial focused ultrasound-mediated neurochemical and functional connectivity changes in deep cortical regions in humans

Low-intensity transcranial ultrasound stimulation (TUS) is an emerging non-invasive technique for focally modulating human brain function. The mechanisms and neurochemical substrates underlying TUS neuromodulation in humans and how these relate to excitation and inhibition are still poorly understood. In 24 healthy controls, we separately stimulated two deep cortical regions and investigated the effects of theta-burst TUS, a protocol shown to increase corticospinal excitability, on the inhibitory neurotransmitter gamma-aminobutyric acid (GABA) and functional connectivity. We show that theta-burst TUS in humans selectively reduces GABA levels in the posterior cingulate, but not the dorsal anterior cingulate cortex. Functional connectivity increased following TUS in both regions. Our findings suggest that TUS changes overall excitability by reducing GABAergic inhibition and that changes in TUS-mediated neuroplasticity last at least 50 mins after stimulation. The difference in TUS effects on the posterior and anterior cingulate could suggest state- or location-dependency of the TUS effect—both mechanisms increasingly recognized to influence the brain’s response to neuromodulation

Pseudo-CTs from T1-weighted MRI for planning of low-intensity transcranial focused ultrasound neuromodulation: An open-source tool

Background: Individual skull models of bone density and geometry are important when planning the expected transcranial ultrasound acoustic field and estimating mechanical and thermal safety in low-intensity transcranial ultrasound stimulation (TUS) studies. Computed tomography (CT) images have typically been used to estimate skull acoustic properties. However, obtaining CT images in research participants may be prohibitive due to exposure to ionising radiation and limited access to CT scanners within research groups. Objective: We present a validated open-source tool for researchers to obtain individual skull estimates from T1-weighted MR images, for use in acoustic simulations. Methods: We refined a previously trained and validated 3D convolutional neural network (CNN) to generate 100 keV pseudo-CTs. The network was pretrained on 110 individuals and refined and tested on a database of 37 healthy control individuals. We compared simulations based on reference CTs to simulations based on our pseudo-CTs and binary skull masks, a common alternative in the absence of CT. Results: Compared with reference CTs, our CNN produced pseudo-CTs with a mean absolute error of 109.8 +/- 13.0 HU across the whole head and 319.3 +/- 31.9 HU in the skull. In acoustic simulations, the focal pressure was statistically equivalent for simulations based on reference CT and pseudo-CT (0.48 +/- 0.04 MPa and 0.50 +/- 0.04 MPa respectively) but not for binary skull masks (0.28 +/- 0.05 MPa). Conclusions: We show that our network can produce pseudo-CT comparable to reference CTs in healthy individuals, and that these can be used in acoustic simulations.Comment: 24 pages, 4 figure

Three-layer model with absorption for conservative estimation of the maximum acoustic transmission coefficient through the human skull for transcranial ultrasound stimulation

Transcranial ultrasound stimulation (TUS) has been shown to be a safe and effective technique for non-invasive superficial and deep brain stimulation. Safe and efficient translation to humans requires estimating the acoustic attenuation of the human skull. Nevertheless, there are no international guidelines for estimating the impact of the skull bone. A tissue independent, arbitrary derating was developed by the U.S. Food and Drug Administration to take into account tissue absorption (0.3 dB/cm-MHz) for diagnostic ultrasound. However, for the case of transcranial ultrasound imaging, the FDA model does not take into account the insertion loss induced by the skull bone, nor the absorption by brain tissue. Therefore, the estimated absorption is overly conservative which could potentially limit TUS applications if the same guidelines were to be adopted. Here we propose a three-layer model including bone absorption to calculate the maximum pressure transmission through the human skull for frequencies ranging between 100 kHz and 1.5 MHz. The calculated pressure transmission decreases with the frequency and the thickness of the bone, with peaks for each thickness corresponding to a multiple of half the wavelength. The 95th percentile maximum transmission was calculated over the accessible surface of 20 human skulls for 12 typical diameters of the ultrasound beam on the skull surface, and varies between 40% and 78%. To facilitate the safe adjustment of the acoustic pressure for short ultrasound pulses, such as transcranial imaging or transcranial ultrasound stimulation, a table summarizes the maximum pressure transmission for each ultrasound beam diameter and each frequency